Well I decided to make a new thread instead, setting it free of the Contador debate.
This is more for the future of the test, and whether we will see this test coming to fruition and being implemented (and reason alone for a 2 year sanction).
The two key articles are:
January 2010: Monfort et al. Urinary di-(2-ethylhexyl)phthalate metabolites in athletes as screening measure for illicit blood doping: a comparison study with patients receiving blood transfusion. Transfusion
December 2010: Solymos et al. Rapid determination of urinary di(2-ethylhexyl) phthalate metabolites based on liquid chromatography/tandem mass spectrometry as a marker for blood transfusion in sports drug testing. Analytical and Bioanalytical Chemistry
From Monfort et al:
What this means is that not only are concentrations much higher in the tranfused than the control, but also the "nontransfused" group who were in contact with medical products (catheters, IVs etc). This is good news as it means there could be a threshold which clearly draws the line between environmental exposure and a transfusion.
Cycling n = 46, Rowing n = 22, Swimming n = 18, Soccer n = 41.
Not just cycling!
The discussion goes on, it mentions that a current problem is that transfusions (homologous) can only be detected in a blood sample (not urine). I think this is an irrelevant point as autologous transfusions are probably a lot more common and they are undetectable in anything - hence that is the bigger problem, not the lack of a urine test.
"Higher environmental exposure" would have to be very high it seems, when all these concentrations were above the control group. Such environmental exposure doesn't seem like the thing which would happen in the middle of an Olympics or Grand Tour.
-Detection window of 24 to 48 hours.
Now this is worrying, it's saying that this test alone shouldn't be grounds for a sanction. The whole reason this test sounds promising is because it could be something in transfusions which is easily detectable, with no microdosing or easy to get around thresholds. If you have to fall back on other tests (like EPO, or biopassport) then it's just not going to be major breakthrough.
From Solymos et al:
100 person control group, 5 person transfusion group (two samples each) and a large doping test athlete group (468).
Note in this study, the 5 patients gave two samples between 0 to 24 hours.
Now I find this confusing. Isn't the idea to use transfusions "in competition" - how many days before or after a race is classified as "out of competition"? Did they go on a training camp near a DEHP factory?
This study also comes to the conclusion that the DEHP test alone is not proof of blood doping.
It also cites other studies which show higher variability amongst the general population - but at most levels they are still below the transfusion concentrations. Also, there is quite a clear distinction between the median concentration for the athletes and the four in the "transfusion zone".
Interesting bit in the conclusion:
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So whilst the results seem promising, both studies paint a gloomy picture by suggesting that the tests could not be standalone proof.
To the cynical eye it would seem quite clearly that a high concentration in a cyclist only has one real explanation and that there's no doubt a positive for DEHP metabolites should be enough to sanction.
I wonder what the process is with WADA and how they work out a legally viable implementation of a new test. i.e. if they heed the advice of these studies there's no way it's good enough, but how hard will WADA work to do their own research and legal work to try and perfect the implementation.
Optimistically, this could actually strengthen the bio passport. The passport is a dead duck as far as getting a sanction is concerned, but maybe this is the final piece of the jigsaw which could make the passport hold up in the courts. Any positive for plasticizer in the middle of a GT would be highly suspicious and if it coincided with a high shift in blood values it could just be enough.
This is more for the future of the test, and whether we will see this test coming to fruition and being implemented (and reason alone for a 2 year sanction).
The two key articles are:
January 2010: Monfort et al. Urinary di-(2-ethylhexyl)phthalate metabolites in athletes as screening measure for illicit blood doping: a comparison study with patients receiving blood transfusion. Transfusion
December 2010: Solymos et al. Rapid determination of urinary di(2-ethylhexyl) phthalate metabolites based on liquid chromatography/tandem mass spectrometry as a marker for blood transfusion in sports drug testing. Analytical and Bioanalytical Chemistry
From Monfort et al:
the concentrations of DEHP metabolites in the urine of transfused subjects was significantly higher than in the control and nontransfused patients groups.
DEHP metabolite concentrations for these subjects were not significantly different from those obtained in the control group
What this means is that not only are concentrations much higher in the tranfused than the control, but also the "nontransfused" group who were in contact with medical products (catheters, IVs etc). This is good news as it means there could be a threshold which clearly draws the line between environmental exposure and a transfusion.
Among athletes, especially high concentrations of DEHP metabolites were found in four samples: one from aquatics, one from cycling, and the other two from soccer (Subjects A, B, C, and D in Table 2). In those samples, concentrations of DEHP metabolites overlapped with some of those obtained in actual patients being transfused.
Cycling n = 46, Rowing n = 22, Swimming n = 18, Soccer n = 41.
Not just cycling!
Recent studies also reflect a steady decrease over recent years of the common exposure to phthalates and this fact further supports that high unexpected concentrations of DEHP metabolites can be easily detected compared with usual urinary background.
The discussion goes on, it mentions that a current problem is that transfusions (homologous) can only be detected in a blood sample (not urine). I think this is an irrelevant point as autologous transfusions are probably a lot more common and they are undetectable in anything - hence that is the bigger problem, not the lack of a urine test.
The appearance of some outliers among athletes (Subjects A, B, C, and D in Table 2) may indicate either a particularly higher environmental exposure than usual or a sudden excretion as a consequence of blood transfusion processes.
"Higher environmental exposure" would have to be very high it seems, when all these concentrations were above the control group. Such environmental exposure doesn't seem like the thing which would happen in the middle of an Olympics or Grand Tour.
-Detection window of 24 to 48 hours.
In our study,medical treatments with PVC devices did not increase the day-long concentrations of DEHP metabolites and, thus, they would not probably explain positive results. Nevertheless, the possibility of other sources of substantial DEHP exposure cannot be completely excluded. For this reason, a close follow-up of any athlete would be needed after any suspicious result of urinary DEHP metabolites concentrations. This follow-up
would include a confirmatory test for allogeneic (or autologous, if the test is available) blood transfusion, and it should also include longitudinal studies to evaluate the normal basal exposure to DEHP of each athlete. The basal
levels of DEHP metabolites may be incorporated as a part of the individual athlete biologic passport, to be able to detect sudden and unexplained increases in DEHP metabolites concentrations in urine that should allow sports authorities to suspect on the misuse of blood transfusions.
Now this is worrying, it's saying that this test alone shouldn't be grounds for a sanction. The whole reason this test sounds promising is because it could be something in transfusions which is easily detectable, with no microdosing or easy to get around thresholds. If you have to fall back on other tests (like EPO, or biopassport) then it's just not going to be major breakthrough.
Compared to other tests that are performed for blood doping detection, such as flow cytometry, the method proposed here is cheaper, less time-consuming, and easy to perform because it is based on liquid chromatography coupled to tandem mass spectrometry technology, nowadays available in all antidoping control laboratories.
From Solymos et al:
100 person control group, 5 person transfusion group (two samples each) and a large doping test athlete group (468).
In comparison to the control group, significantly higher concentrations of the secondary DEHP metabolites were observed in urine samples received after blood transfusion (Fig. 3). The maximum concentrations of 5oxo-MEHP and 5OH-MEHP in the control samples were 18- and 13-fold lower as the minimum concentrations determined after transfusion (Table 4). The 99.9% upper reference values of the control group were determined at 54.4 ng/mL for 5oxo-MEHP and 94.8 ng/mL for 5OHMEHP which are 12- and 9-fold lower than the lowest value measured after blood transfusion.
Note in this study, the 5 patients gave two samples between 0 to 24 hours.
Three out of four outliers were taken out-of competition at the same time originating from one cycling team.
Now I find this confusing. Isn't the idea to use transfusions "in competition" - how many days before or after a race is classified as "out of competition"? Did they go on a training camp near a DEHP factory?
This study also comes to the conclusion that the DEHP test alone is not proof of blood doping.
It also cites other studies which show higher variability amongst the general population - but at most levels they are still below the transfusion concentrations. Also, there is quite a clear distinction between the median concentration for the athletes and the four in the "transfusion zone".
Interesting bit in the conclusion:
Currently, the presented assay covers only DEHP. However, an implementation of alternatively used plasticizers in blood bags or other medical devices seems to be promising, assuming comparable physical properties of used substances. As a future prospect, the applicability of the method on different plasticizers has to be investigated
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So whilst the results seem promising, both studies paint a gloomy picture by suggesting that the tests could not be standalone proof.
To the cynical eye it would seem quite clearly that a high concentration in a cyclist only has one real explanation and that there's no doubt a positive for DEHP metabolites should be enough to sanction.
I wonder what the process is with WADA and how they work out a legally viable implementation of a new test. i.e. if they heed the advice of these studies there's no way it's good enough, but how hard will WADA work to do their own research and legal work to try and perfect the implementation.
Optimistically, this could actually strengthen the bio passport. The passport is a dead duck as far as getting a sanction is concerned, but maybe this is the final piece of the jigsaw which could make the passport hold up in the courts. Any positive for plasticizer in the middle of a GT would be highly suspicious and if it coincided with a high shift in blood values it could just be enough.